{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T01:21:19Z","timestamp":1787620879110,"version":"build-2736575974"},"reference-count":46,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,5,30]],"date-time":"2013-05-30T00:00:00Z","timestamp":1369872000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2013,6]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To examine the role of immune dysregulation in antibiotic\u2010refractory Lyme arthritis by comparing the phenotype, frequency, and function of CD4+ Teff cells and Treg cells in patients with antibiotic\u2010 responsive arthritis and patients with antibiotic\u2010refractory arthritis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Matched peripheral blood and synovial fluid samples from 15 patients with antibiotic\u2010responsive arthritis were compared with those from 16 patients with antibiotic\u2010refractory arthritis, using flow cytometry, suppression assays, and cytokine assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Critical differences between the 2 patient groups were observed in the synovial fluid CD4+CD25\n                      <jats:sup>high<\/jats:sup>\n                      population, a cell subset usually composed of FoxP3\u2010positive Treg cells. In patients with antibiotic\u2010refractory arthritis, this cell population often had fewer FoxP3\u2010positive cells and a greater frequency of FoxP3\u2010negative (Teff) cells compared with patients with antibiotic\u2010responsive arthritis. Moreover, the expression of glucocorticoid\u2010induced tumor necrosis factor receptor and OX40 on CD4+CD25\n                      <jats:sup>high<\/jats:sup>\n                      cells was significantly higher in the antibiotic\u2010refractory group. Suppression assays showed that CD4+CD25\n                      <jats:sup>high<\/jats:sup>\n                      cells in patients with antibiotic\u2010refractory arthritis did not effectively suppress proliferation of CD4+CD25\u2212 cells or secretion of interferon\u2010\u03b3 and tumor necrosis factor \u03b1, whereas those cells in patients with antibiotic\u2010responsive arthritis did suppress proliferation of CD4+CD25\u2212 cells and secretion of interferon\u2010\u03b3 and tumor necrosis factor \u03b1. Finally, in the antibiotic\u2010refractory group, higher ratios of CD25\n                      <jats:sup>high<\/jats:sup>\n                      FoxP3\u2010negative cells to CD25\n                      <jats:sup>high<\/jats:sup>\n                      FoxP3\u2010positive cells correlated directly with a longer duration of arthritis after antibiotic treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Patients with antibiotic\u2010refractory Lyme arthritis often have lower frequencies of Treg cells, higher expression of activation coreceptors, and less effective inhibition of proinflammatory cytokines. This suggests that immune responses in these patients are excessively amplified, leading to immune dysregulation and antibiotic\u2010refractory arthritis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.37910","type":"journal-article","created":{"date-parts":[[2013,3,1]],"date-time":"2013-03-01T06:33:23Z","timestamp":1362119603000},"page":"1643-1653","source":"Crossref","is-referenced-by-count":63,"title":["Dysregulation of CD4+CD25\n                    <sup>high<\/sup>\n                    T Cells in the Synovial Fluid of Patients With Antibiotic\u2010Refractory Lyme Arthritis"],"prefix":"10.1002","volume":"65","author":[{"given":"Nalini K.","family":"Vudattu","sequence":"first","affiliation":[{"name":"Massachusetts General Hospital and Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klemen","family":"Strle","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital and Harvard Medical 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